The overall UW ACE theme centers on a comprehensive developmental model of risk, risk processes, symptom emergence, and adaptation in autism spectrum disorder (ASD). According to this model, early autism risk factors (genetic/familial and environmental) lead to risk processes, namely, altered patterns of interaction between the child and his/her environment, which contribute to the abnormal development of neural circuitry and atypical behaviors. This project examines the interaction between genetic and child phenotypic risk factors and family processes in determining outcome in autism. Outcome will be examined not only in terms of core symptoms, but also in terms of associated symptoms, including repetitive and stereotyped behaviors, hyperactivity, and externalizing and internalizing behaviors. These associated symptoms have a significant impact on both the child and family, and are a common focus of therapeutic interventions. As such, there is a pressing need for longitudinal studies to determine risk and protective factors related to the development of associated symptoms. Project V incorporates two longitudinal follow-up studies of children with ASD to address two broad aims. First, in a prospective longitudinal cohort study of children who are transitioning into adolescence, we will investigate the role of genetic, child phenotypic, and family risk and protective factors in development of associated symptoms. Second, in a younger longitudinal cohort, we will conduct a follow-up study of a randomized, controlled trial of early intensive behavioral intervention to examine the long term effects on both core and associated symptoms. We will test hypotheses regarding potential moderators and mediators of long term effects. This proposal directly addresses goals outlined in the NIH Autism Research Matrix, including the evaluation of intervention strategies and the follow-up of early intervention. The identification of risk and protective factors related to long term outcome, including the development of associated symptoms, will yield important insights into autism, and will inform the critical targets for therapeutic intervention for affected children and families.